Hodgkin lymphoma (HL) is a neoplasm of lymphoid tissue that is defined histopathologically by the presence of the malignant Hodgkin-Reed-Sternberg (HRS) cells. The characteristic surface antigen expressed on HRS cells is CD30. There are an estimated 8,000 new HL cases diagnosed annually in the United States and Canada. Advances in the use of combined chemotherapy and radiotherapy in HL over the past half-century have resulted in a durable remission rate of approximately 70%. However, these multi-agent regimens confer a significant morbidity on patients, including secondary malignancies, cardiac disease, and infertility. Furthermore, approximately 30% of patients presenting with HL will become refractory to initial therapy or will relapse. Salvage chemotherapy regimens and autologous stem cell transplant (ASCT) are secondary options for these patients, but both are associated with significant morbidity and limited long term disease control. Patients who relapse after ASCT or are ineligible for salvage therapy have a very poor prognosis. Currently, there is a lack of well-tolerated, efficacious treatment options for these patients.
Gemcitabine, alone or in combination with other chemotherapy, has been evaluated in the pre and post-ASCT setting. In the transplant naïve setting, relapsed or refractory HL patients treated with gemcitabine achieve response rates of 39% (Santoro et al., J Clin Oncol 2000 18(13):2615-9). In the relapsed/refractory setting where the majority of patients have received prior autologous or allogeneic transplant, gemcitabine response rates are diminished (22%) and hematologic toxicity of the regimen necessitates dose reduction to 1000 mg/m2 (Venkatesh et al., Clin lymphoma 2004 5(2):110-5). A combination regimen utilizing gemcitabine, vinorelbine and pegylated liposomal doxorubicin (GVD) has demonstrated promising efficacy in relapsed/refractory HL. Overall response rates of 70% were observed in the combined analysis of pre and post-ASCT patients, however with dose limiting toxicities of mucositis in the pre-ASCT population and febrile neutropenia in the post-ASCT population (Bartlett al., CALGB 59804 Ann Oncoo, 2007 18(6): 1071-9). Only 32% and 26% of patients who were transplant naïve and post-ASCT, respectively, were able to receive all doses on schedule at full dose. For patients who do not respond to standard chemotherapy or who relapse, the only potentially curative therapy is high-dose chemotherapy in combination with stem cell transplantation. This treatment is also associated with significant morbidity and mortality, and a 5-year survival rate of less than 50%. Thus, there continues to be an unmet medical need for patients suffering from HL. The present invention addresses this and other needs.